2-72592896-C-G

Variant names:

• chr2-72592896-C-G
• rs1446893
• NM_015189.3:c.670-17228G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015189.3(EXOC6B):​c.670-17228G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,212 control chromosomes in the GnomAD database, including 65,055 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (65055 hom., cov: 31)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 0 publications found

Genes affected

EXOC6B (HGNC:17085): (exocyst complex component 6B) This gene encodes a protein which is a part of the evolutionarily conserved exocyst, a multimeric protein complex necessary for exocytosis, which in turn, is crucial for cell growth, polarity and migration. Disruption of this gene may be associated with phenotypes exhibiting multiple symptoms including intellectual disability and developmental delay (DD). [provided by RefSeq, Jun 2016]

EXOC6B Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia with joint laxity, type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia with joint laxity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015189.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6B	NM_015189.3	MANE Select	c.670-17228G>C		intron	N/A	NP_056004.1	Q9Y2D4-1
	EXOC6B	NM_001321729.2		c.670-17228G>C		intron	N/A	NP_001308658.1	A0A0U1RRB6
	EXOC6B	NM_001321731.2		c.670-17228G>C		intron	N/A	NP_001308660.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6B	ENST00000272427.11	TSL:1 MANE Select	c.670-17228G>C		intron	N/A	ENSP00000272427.7	Q9Y2D4-1
	EXOC6B	ENST00000410104.1	TSL:1	c.670-17228G>C		intron	N/A	ENSP00000386698.1	J3QT38
	EXOC6B	ENST00000971151.1		c.742-17228G>C		intron	N/A	ENSP00000641210.1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140519 AN: 152094 Hom.: 64999 Cov.: 31

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.903

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.924 AC: 140633 AN: 152212 Hom.: 65055 Cov.: 31 AF XY: 0.926 AC XY: 68890 AN XY: 74418

African (AFR) AF: 0.971 AC: 40336 AN: 41532

American (AMR) AF: 0.927 AC: 14161 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3207 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5146 AN: 5178

South Asian (SAS) AF: 0.930 AC: 4479 AN: 4814

European-Finnish (FIN) AF: 0.916 AC: 9707 AN: 10596

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60685 AN: 68020

Other (OTH) AF: 0.899 AC: 1899 AN: 2112

Alfa AF: 0.902 Hom.: 3429

Bravo AF: 0.926

Asia WGS AF: 0.955 AC: 3323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.61
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1446893; hg19: chr2-72820025;